Introduction

Patients with an ileostomy may experience postoperative electrolyte derangement and dehydration but are presumed to stabilise thereafter.

Aims & Methods

We aimed to investigate the prevalence of sodium depletion in stable outpatients with an ileostomy and applied established methods to estimate their fluid status.
We invited 178 patients with an ileostomy through a region-wide Quality-of-Life-survey to undergo outpatient evaluation of their sodium and fluid status. The patients delivered urine and blood samples, had bioelectrical impedance analysis performed, and answered a questionnaire regarding dietary habits.

Results

Out of 178 invitees, 49 patients with an ileostomy were included; 22 patients (45%, 95% CI, 31-59%) had unmeasurably low urinary sodium excretion (<20 mmol/L), indicative of chronic sodium depletion, and 26% (95% CI, 16-41%) had plasma aldosterone levels above the reference value. Patients with unmeasurably low urinary sodium excretion had low estimated glomerular filtration rates (median 76, IQR 63-89, mL/min/1.73m²) and low venous blood plasma CO₂ (median 24, IQR 21-26, mmol/L), indicative of chronic renal impairment and metabolic acidosis. Bioelectrical impedance analysis, plasma osmolality, creatinine and sodium values were not informative in determining sodium status in this population.

Conclusion

A high proportion of patients with an ileostomy may be chronically sodium depleted, indicated by absent urinary sodium excretion, secondary hyperaldosteronism, and chronic renal impairment, despite normal standard biochemical tests. Sodium depletion may adversely affect longstanding renal function. Future studies should investigate methods to estimate and monitor fluid status and aim to develop treatments to improve sodium depletion and dehydration in patients with an ileostomy.

Introduction

Guselkumab (GUS) intravenous (IV) induction followed by subcutaneous (SC) maintenance with 200mg q4w or 100mg q8w was effective in the GALAXI 2 & 3 phase 3 treat-through studies of participants (pts) with moderately to severely active Crohn’s disease (CD), with similar efficacy between both maintenance doses in the overall study populations. Here, we evaluated the efficacy of maintenance doses in subgroups by baseline disease activity and severity and inflammatory burden at Week (Wk) 12 to determine if some pts may receive additional benefit from the higher maintenance dose.

Aims & Methods

Eligible pts had moderately to severely active CD (CDAI 220–450 and mean daily stool frequency score >3 or abdominal pain score >1), SES-CD ≥6 (≥4 for isolated ileal disease), and inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics. Pts were randomly assigned to GUS 200mg IV at Wks 0, 4, and 8, followed by GUS SC 100mg q8w (N=286) or 200mg q4w (N=296). The studies also included placebo and ustekinumab arms, but this analysis focused on differences between GUS maintenance doses. Wk48 endpoints included clinical remission (CDAI <150) and endoscopic response (≥50% improvement in SES-CD or SES-CD ≤2). Analyses of subgroups by baseline disease activity (CDAI >300 or SES-CD >12), and inflammatory burden (CRP >5) or endoscopic response at Wk 12 were prespecified but not multiplicity controlled.

Results

In the pooled GALAXI 2 & 3 dataset, pts with baseline high disease activity (CDAI >300 or SES-CD >12) had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg q4w compared with 100mg q8w. Pts with baseline CDAI >300 had numerically greater percentages of clinical remission (200mg: 68.0% [83/122] vs 100mg: 55.1% [65/118], respectively) and endoscopic response (52.5% [64/122] vs 44.1% [52/118]) at Wk 48. Pts with baseline SES-CD >12 also had numerically greater percentages of these outcomes (clinical remission: 77.0% [94/122] vs 65.1% [82/126] and endoscopic response 67.2% [82/122] vs 58.7% [74/126]). Pts with baseline CDAI ≤300 or SES-CD ≤12 had similar Wk 48 outcomes for both maintenance doses. Pts with greater inflammatory burden (CRP >5mg/L) at Wk 12 or who were not in endoscopic response at Wk 12 also had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg compared with 100mg (Table). Pts with CRP ≤5mg/L or who were in endoscopic response at Wk 12 had similar clinical and endoscopic outcomes for both maintenance doses. Results for individual GALAXI 2 & 3 studies generally trended in the same direction for all subgroups.

Conclusion

Pts with high clinical or endoscopic disease severity at baseline, greater inflammatory burden after induction, or who had not achieved endoscopic response after induction showed greater clinical and endoscopic outcomes at Wk 48 with GUS 200mg SC q4w compared with 100mg SC q8w.

Disclosure

AA: AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Johnson & Johnson, Pfizer, Takeda, and TLL Pharmaceuticals
TH: grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
DTR: consulting/speaker fees/advisory board for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; membership on Board of Directors of Cornerstones Health, Inc and Crohn’s & Colitis Foundation’s Board of Trustees.
NAT, RVR, JY, KYYW, and ZY: employees of and may own Johnson & Johnson stock.
WR: speaker for AbbVie, Celltrion, Ferring, Johnson & Johnson, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Johnson & Johnson, Medahead, Microbiotica, Pfizer, Takeda; advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Johnson & Johnson, Pfizer; funding from AbbVie, Johnson & Johnson, Sandoz, Sanofi, Takeda.
BES: consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics; consulting /speaking fees from Abivax; consulting/speaking fees/other support from Lilly; research grants/consulting/speaking fees/other support from Bristol Myers Squibb, Johnson & Johnson, Pfizer, and Takeda; stock/options from Ventyx Biopharma.
SD: consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
RP: consulting fees from Abbivax, Abbott, AbbVie, Alimentiv, Amgen, AnaptsyBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Spyre Therapeutics, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Johnson & Johnson, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; Advisory Boards for AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.

Introduction

The evidence on efficacy of vaccination given to children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is missing.

Aims & Methods

The aim of our study was to assess serologic response to vaccination in children exposed prenatally to this medication due to inflammatory bowel disease (IBD) of their mothers. Children ≥ 1 year of age exposed to UST or VDZ in utero who had completed at least 1 year mandatory vaccination were included. Serological response to the following vaccination was assessed: non-live vaccines: tetanus, diphtheria; live-vaccines: mumps, rubella, measles. Data on perinatal period were collected using predefined questionnaire filled by mother and/or treating physician and supplied from patient medical files. Information on cord blood levels of biologics were retrieved from patients' medical files.

Results

Twenty-one children were included, 10 exposed to VDZ and 11 to UST. Median age at blood sampling was 26 months (range: 13-49). Except one child exposed to VDZ, all children were born at term with median birth weight of 3250 g (range: 650 - 4000) with 3 (14%) infants having low birth weight. Median gestational week of the last drug administration was week 31 and week 30 in case of VDZ and UST, respectively. Cord levels were measured in 7 VDZ and 10 UST- exposed infants with median (range) cord blood levels of 5.3 mg/l (1.1-21.3) and 2.4 mg/l (0.4-30), respectively. Results on serologic response to vaccination are outlined in Table 1. Tetanus, diphtheria, rubella and measles vaccines demonstrated adequate serologic response in ≥ 80% of children exposed either to VDZ or UST. Regarding mumps lower serologic response was found in children exposed to UST (62.5%), with all infants exposed to VDZ responding adequately.

Table 1. Adequate serologic response to vaccination

Conclusion

Despite the limited sample size, most of the infants exposed to VDZ or UST in utero were successfully immunised to non-live (tetanus, diphtheria) and live vaccines. Somewhat lower rate of adequate serologic response to mumps in UST group is in line with previous report of anti-TNFa exposed infants and their controls (1). There is a need for a control group of unexposed children to make comparison.

References

Duricova D. et al. Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long-term Outcome of Exposed Children: A Controlled, Multicenter Observation. Inflamm Bowel Dis 2019; 14;25(4):789-796.

Disclosure

The study was supported by IBD-Comfort foundation.

Introduction

Functional Defecation Disorders (FDD) are a frequent cause of refractory chronic constipation (CC). FDD diagnosis requires focused anorectal physiology testing, which is not easily available outside referral centers. Therefore, easy-to-perform tools to select patients needing anorectal physiology testing would be very welcome.

Aims & Methods

Our aim was to evaluate accuracy and Odds Ratio (OR) of a straining questionnaire (SQ) and a digital rectal examination augmented by abdomen palpation on straining (augmented-DRE) on predicting a FDD in refractory CC patients.
Two-hundred and thirty-eight CC patients failing a 4-week conservative treatment were enrolled. A SQ (Which muscles do you mainly use when you push to defecate?) was administered to all patients before entering the study (T0) and after a 30-day fiber/laxative trial (T30). The possible answers were: “belly muscles”; “anal muscles”; “both”; “Don’t know/No answer”.
Augmented-DRE and BET were performed at T0 and at T30.
At T30, all patients underwent anorectal manometry.
OR and accuracy were calculated for SQ, augmented-DRE and combinations in predicting and diagnosing both dyssynergic defecation (DD) and inadequate defecatory propulsion (IDP).
Sixty-one healthy volunteers (HVs) underwent SQ and BET.

Results

One-hundred and twenty patients showed features of Rome III FDD: 82 DD and 38 IDP.
“Anal Muscles” response was associated to both DD and IDP, with an OR of 13.6 and 5.85 (p<0.001) and an accuracy of 78.5% and 66.4%, respectively.
“Failed anal relaxation” on augmented-DRE was associated with a DD, with an OR of 21.4 and an accuracy of 73.1%. “Failed abdominal contraction” on augmented-DRE was associated with an IDP with an OR>100 and an accuracy of 97.1%.
SQ and augmented-DRE were reproducible between T0 and T30 (k=0.97 and k=0.517, respectively).
Regarding combinations of SQ and augmented-DRE, the combination increased the accuracy of the diagnostic tool for DD compared to SQ or augmented-DRE alone (Table-1).
All HVs had a negative BET and one answered SQ with “Anal strain”.

Table-1 – Accuracy and diagnostic test evaluator of SQ and augmented-DRE in predicting and diagnosing FDD

Conclusion

Our data support screening CC patients for DD and IDP, at all levels of care, by SQ and augmented-DRE, to improve the management and appropriateness of the referral to anorectal physiology testing.

Introduction

During and following the COVID-19 pandemic, there has been a major expansion of self-administered subcutaneous biologics for the management of inflammatory bowel disease. These agents are more difficult to monitor since patients do not need to attend the Biologics infusion unit and there is no audit trail to confirm administration of the drug at the scheduled time points.

Aims & Methods

Following a successful NHS D&I bid for funding, a pilot proof of concept project to assess the feasibility and uptake of a digital technology (Health Beacon Digital Sharps Box®) to record and monitor subcutaneous injectable pen use was implemented in 50 consecutive IBD patients who were being treated with subcutaneous infliximab (Remsima®), Adalimumab (Amgevita®) or Vedolizumab (Entyvio®), on a 2-weekly schedule. The Health Beacon ICMS is comprised of a Smart Sharps Bin, pre-programmed with a patient’s individual treatment schedule. The bin electronically captures each time a used injection is disposed of, to create a time-stamped record as a proxy for medication adherence. This is accompanied by Health Beacon’s Companion App and Care Team support. Patients were also sent electronic dose reminders if they failed to dispose of a scheduled injection within certain time periods. Adherence data from the HealthBeacon ICMS, as well as patient satisfaction, transmission reports of data to

Results

Of 50 patients invited to join the programme, 45 registered patients had complete record of 6 months follow up; 4 patients deactivated recruitment and 1 left the programme. 21 patients were on Vedolizumab, 18 on Adalimumab and 8 on Infliximab, all 2-weekly SC injection. 45% patients were in the 36-50year age group, with the remaining spread between 18-75 years. M: F=21:24. Of 418 scheduled drops, 360 were made, with overall adherence being 86%. On time adherence was 76%. The study showed that up to 24% pts on SC Biologics at home delay their scheduled drug administration. Patient satisfaction was high. Reasons for delay in administration included forgetting, being away from home and being busy. Reminders were acknowledged.

Conclusion

This is the first study to our knowledge exploring adherence to subcutaneous biologics at home for IBD. It showed that a digital injection monitoring and support system is useful and acceptable to track adherence. Of the patients involved in the study there is an overall adherence of 90%, with up to 24% patients delaying their scheduled administration. Further studies are needed to analyse patient behaviour and impact on disease course.

Disclosure

Anjan Dhar has been paid an honorarium as a Speaker for presenting this abstract the a Health Beacon Meeting